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NON-SMALL CELL LUNG CANCER OVERVIEW — Non-small cell lung cancer (NSCLC) accounts for between 85 and 90 percent of all lung cancers; the remaining 10 to 15 percent are small cell lung cancers. This distinction is important when considering treatment.
This article will discuss the treatment of stage IV (advanced) NSCLC, in which the cancer has spread (or metastasized) beyond the initial location. Stage IV NSCLC includes cancers that have spread to areas beyond the chest, like the brain (figure 1). Stage IV cancer also includes people who have a fluid collection around the lung (called a malignant pleural effusion) caused by the cancer.
Stage IV NSCLC cannot be cured, but treatment can reduce pain, ease breathing, and extend and improve quality of life.
The treatment of earlier-stage NSCLC is discussed separately. The risks, symptoms, and diagnosis of NSCLC are also discussed separately. (See "Patient education: Non-small cell lung cancer treatment; stage I to III cancer (Beyond the Basics)" and "Patient education: Lung cancer risks, symptoms, and diagnosis (Beyond the Basics)".)
More detailed information about lung cancer, written for health care providers, is available by subscription. (See 'Professional-level information' below.)
CANCER CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history of cancer.
In some cases, if you live in an area with a lot of cases of COVID-19, your doctor might suggest rescheduling or delaying medical appointments. But this decision must be balanced against the importance of getting care to screen for, monitor, and treat cancer. Your doctor can talk to you about whether to make any changes to your appointment schedule. They can also advise you on what to do if you test positive or were exposed to the virus.
PERSONALIZED TREATMENT — An improved understanding of the biology and genetics of non-small cell lung cancer (NSCLC) has led to the recognition that different treatment approaches may be needed depending on the person and the characteristics of the cancer.
In many cases, doctors can identify specific genetic abnormalities (mutations) through an analysis of the DNA from the tumor. New treatments developed to specifically address these abnormalities are referred to as "targeted therapy" (see 'Targeted therapy' below). When no mutation is found, immunotherapy with or without chemotherapy is usually the recommended treatment approach (see 'Immunotherapy' below and 'Chemotherapy' below). Surgery might be an option in some patients if the cancer has spread to a single place outside the lung.
In general, treatment for stage IV NSCLC involves the sequential use of a number of different therapies. The decision about which therapies to use depends on your situation (including your age, history, overall health, and preferences) as well as the characteristics of your cancer and where and how extensively it has spread. The goals of treatment are to prolong survival, ease symptoms, and improve or maintain quality of life.
TARGETED THERAPY — Targeted therapy describes treatments that interfere with how a cancer grows and spreads when a specific abnormality is present. These treatments work in a different way than standard chemotherapy.
In order to know whether you might benefit from targeted therapy, a sample of your tumor (obtained by surgery or biopsy) is analyzed in a laboratory to look for certain abnormalities (mutations). Tests on your tumor (or in some cases, blood tests) can determine whether your cancer belongs to one of the categories that is likely to respond to targeted therapy:
●Epidermal growth factor receptor (EGFR) mutations – The EGFR is a protein that sometimes has a particular mutation that can stimulate growth and spread of the cancer. If this mutation is found, targeted therapy is generally used instead of standard chemotherapy. People in this category are usually treated with a type of drug called a tyrosine kinase inhibitor (TKI). The preferred TKI is osimertinib (brand name: Tagrisso), although others are available. The most common side effects of TKIs are skin rash and diarrhea.
●Anaplastic lymphoma kinase (ALK) gene abnormalities – An abnormal fusion (combination) of the ALK gene with another gene can drive the growth of some non-small cell lung cancers (NSCLCs). Alectinib (brand name: Alecensa) is a targeted medicine that may be more effective than standard chemotherapy in this situation. Other medicines that act in a similar way may be appropriate alternatives. Alectinib is generally well tolerated, but can cause constipation and myalgias.
●ROS1 abnormalities – An abnormality in the ROS1 gene is present in another set of patients with NSCLC. Crizotinib (brand name: Xalkori) has been found to be effective in many people in this group as well.
●Other specific abnormalities (such as mutations in the HER2, BRAF, RET, TRK, MET, or KRAS genes) may be suitable for specific targeted treatments, and other mutations are being identified. In some cases, you may want to consider participating in a clinical trial of new drugs if your tumor contains one of these abnormalities.
If your initial treatment with a targeted agent does not work, or if you initially respond and then your disease progresses, your doctor may recommend treatment with chemotherapy. Other targeted therapy options are being studied as well.
IMMUNOTHERAPY — If you do not have a mutation that makes you a candidate for targeted therapy, immunotherapy will likely be a part of your treatment. Immunotherapy is a type of treatment that uses the body's immune system to help slow or stop cancer growth.
Various forms of immunotherapy are being developed to help the body recognize a tumor as being different from normal tissues in the body. One of these immunotherapy approaches is a group of medications called checkpoint inhibitors. "Checkpoints" are a built-in part of the immune system intended to prevent it from attacking healthy cells. Cancer takes advantage of this system to prevent the body from attacking cancer cells, even though they are abnormal cells. Checkpoint inhibitors act on the body's lymphocytes (a type of white blood cell normally involved in fighting infections) to allow them to identify and destroy cancer cells.
How immunotherapy will be incorporated into your treatment depends on how much of a protein called "programmed cell death ligand-1 (PD-L1)" is present in your cancer. If the level is high (ie, the protein is present in more than 50 percent of the cancer cells in your body), your doctor may suggest initial treatment with immunotherapy alone. If your PD-L1 expression level is low (ie, the protein is present in less than 50 percent of cancer cells), or if your cancer is progressing very quickly, you might get treatment with pembrolizumab along with chemotherapy. (See 'Chemotherapy' below.)
The side effects of immunotherapy are related to its actions that allow the immune system to attack cancerous tissue. This can affect normal (healthy) tissue as well; as a result, a variety of side effects can occur, including skin reactions, colitis (inflammation of the colon), pneumonitis (inflammation of the lungs), and endocrine disorders such as thyroid disease.
CHEMOTHERAPY — Chemotherapy may be used as a first-line treatment, along with immunotherapy (see 'Immunotherapy' above) in certain situations, or if your cancer progresses following immunotherapy or targeted therapy. (See 'Targeted therapy' above.)
Chemotherapy is given to slow or stop the growth of cancer cells at least temporarily. It is not given every day, but instead is given in cycles. A cycle of chemotherapy (typically about 21 days) refers to the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines. Your health care provider can describe which chemotherapy drugs will be needed.
Most initial chemotherapy treatments involve a combination (regimen) of two chemotherapy drugs. The most commonly used regimens include either cisplatin (brand name: Platinol) or carboplatin (brand name: Paraplatin); this is combined with one of several other chemotherapy drugs.
Most of the drugs are given by IV (through a vein) once every three weeks.
Four to six cycles of chemotherapy are usually recommended, depending upon your response to treatment. In many cases, your doctor may recommend continuation of treatment with one drug after the four cycles of chemotherapy if you have had a favorable response to the initial treatment.
If your initial chemotherapy treatment does not work, or if you initially respond and then have progressive disease, your doctor may recommend other treatment, with immunotherapy, chemotherapy, or a targeted agent.
Side effects — The most serious side effect of chemotherapy is a temporary drop in your blood count. This can increase your risk of developing an infection. Blood counts typically fall 7 to 14 days after the chemotherapy is given. During this time, you should call your doctor or nurse immediately if you develop chills or have a fever (temperature higher than 100.4ºF or 38ºC).
A number of other side effects are possible and these include:
●Temporary hair loss
●Numbness in the fingers and toes (called neuropathy)
●Nausea and vomiting
●Skin rash
Treatment for older people and those who are ill — Some people are not healthy enough to have a chemotherapy regimen with two drugs as described above. This might include people who are older or who have another serious illness. In this case, treatment with one chemotherapy medicine (rather than two) or with a targeted therapy (see 'Targeted therapy' above) may be an option, depending on the situation. This type of treatment can prolong survival and improve quality of life. The side effects of one chemotherapy medicine are not as severe as when two are used.
TREATMENT OF METASTASES IN NON-SMALL CELL LUNG CANCER — The brain, the bones, and the area around the lungs (the pleural space) are common places for cancer to spread ("metastasize") in people with non-small cell lung cancer (NSCLC). Cancer that has spread from the lungs to the brain or bones is called metastatic lung cancer, not brain cancer or bone cancer.
In some cases, certain areas of spread require particular treatment directed toward the metastases.
Malignant pleural effusion — A pleural effusion is a collection of fluid in the chest that is located in the pleural space, a pocket between the lung and the tissues of the chest wall (figure 1). This space is normally empty, although it can accumulate fluid in people with advanced lung cancer. The fluid pushes against the lung, compressing it and preventing the lung from fully expanding when breathing. Thus, the most common symptom of a pleural effusion is shortness of breath.
In most people with advanced lung cancer, the pleural effusion is caused by the cancer. This is called a malignant pleural effusion.
Treatment of the pleural effusion is usually recommended for people who develop shortness of breath. Shortness of breath often worsens as more fluid accumulates.
The simplest way to treat a pleural effusion is to insert a small tube (a catheter) into the space around the lung and allow the fluid to drain out. Afterward, the catheter is removed. This is called a thoracentesis. Thoracentesis can usually be done in the office or hospital room using local anesthesia (ie, numbing the area where the catheter is inserted).
If the fluid reaccumulates quickly, meaning that you need another thoracentesis in less than one month, a more aggressive treatment might be recommended. This includes a catheter that is left in place (a tunneled catheter) or using a substance to block the build-up of fluid (called pleurodesis).
●Tunneled catheter – Some people are treated with a catheter that is left in the pleural space and connected to a container. This is called a tunneled catheter. The patient (or a family member) uses a vacuum bottle to drain the fluid once a day or as needed. The catheter is usually inserted during a day (outpatient) surgery procedure. It is left in place for several weeks or months, as long as the fluid continues to drain. The advantage of a catheter over other treatments is that it allows the patient and their doctors to manage the fluid collection out of the hospital.
●Pleurodesis – Another option for treating a malignant effusion is called chemical pleurodesis. This involves draining the fluid and then applying a substance (usually talcum powder) to the surface of the lung, which helps prevent the fluid from collecting again. This treatment is usually done in the hospital and requires a three- to five-day stay. It may be associated with temporary pain and fever for a few days.
Brain metastases — Symptoms of brain metastases can include:
●Headache (often in the morning)
●Weakness (which can affect the arms or legs)
●Vision changes
●Trouble thinking clearly
●Seizures (convulsions)
If your doctor is concerned about brain metastasis, he or she will order a magnetic resonance imaging (MRI) study or computed tomography (CT) scan. Treatments for brain metastases include radiation therapy and medicines to reduce brain swelling (steroids).
People who have one or a small number of metastases in the brain are sometimes offered more aggressive treatment. This might include surgery to remove tumor(s) in the brain. Stereotactic radiosurgery (also called the gamma knife) is an alternative to surgery in selected patients. Stereotactic radiosurgery uses high doses of radiation in a small area given in a small number of treatments. Both surgery and stereotactic radiosurgery are often combined with radiation therapy to the entire brain to prevent the regrowth of the cancer in the brain. However, some people may be offered targeted therapy or immunotherapy alone, without surgery or radiation, for brain metastases. The choice of therapy depends on the extent of the disease of the brain as well as the characteristics of the cancer.
Bone metastases — Bone metastases, the spread of lung cancer to one or more bones, can cause pain or fractures. There are several options for treating bone metastases: targeted therapy, chemotherapy, radiation therapy, and a medicine called a bisphosphonate.
●Targeted therapy or chemotherapy can often shrink or slow the growth of bone metastases, since these medicines act throughout the body. (See 'Targeted therapy' above and 'Chemotherapy' above.)
●Radiation therapy can reduce bone pain caused by metastases. This treatment is a good option for people with severe bone pain caused by metastasis in one or a limited number of areas. The treatment usually begins to relieve pain within one week after treatment. The treatment is given in one or a few doses, similar to having an X-ray.
●Medicine (either a bisphosphonate or denosumab) might be used to prevent bone-metastasis-related problems, like fractures and bone loss. If your caregiver recommends this treatment, you should have any important dental work done first. There is a risk of a serious problem in the jaw bone related to dental work done after treatment when these drugs are used to treat bone metastases.
Oligometastases — Some patients have only a small number of metastases affecting only a few parts of the body. When the extent of metastatic cancer is limited in this manner, it is called "oligometastatic." Treatments including radiation therapy can help some people with oligometastatic disease live longer.
PALLIATIVE CARE — Stage IV lung cancer cannot be cured. However, early integration of palliative care (also called "comfort care") into the treatment of advanced non-small cell lung cancer (NSCLC) may improve quality of life. This can include assessment of physical and psychological needs and the goals for care.
Deciding when to stop treating the cancer can be difficult and should involve you as well as your family, friends, and health care team. Ending cancer treatment does not mean ending care. Hospice care is frequently recommended when a person is unlikely to live longer than six months. Hospice care involves treatment of all aspects of a person's and family's needs, including the physical (eg, pain relief), psychological, social, and spiritual aspects of suffering. This care can be given at home or in a nursing home or hospice facility and usually involves multiple care providers, including a doctor, registered nurse, nursing aide, a chaplain or religious leader, a social worker, and volunteers.
These providers work together to meet the patient's and family's needs and significantly reduce their suffering. Your health care team can give you more information about hospice care.
CLINICAL TRIALS — Progress in treating lung cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:
●www.cancer.gov/clinicaltrials/
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (http://www.cancer.net/pre-act).
WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.
Patient-level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Lung cancer (The Basics)
Patient education: Non-small cell lung cancer (The Basics)
Patient education: Lung cancer screening (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Non-small cell lung cancer treatment; stage I to III cancer (Beyond the Basics)
Professional-level information — Professional-level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional-level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Overview of the initial treatment and prognosis of lung cancer
Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer
Overview of the initial treatment of advanced non-small cell lung cancer
Personalized, genotype-directed therapy for advanced non-small cell lung cancer
Systemic therapy for advanced non-small cell lung cancer with an activating mutation in the epidermal growth factor receptor
Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer
Systemic chemotherapy for advanced non-small cell lung cancer
Epidemiology, clinical manifestations, and diagnosis of brain metastases
Radiation therapy for the management of painful bone metastases
Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors
Management of malignant pleural effusions
Hospice: Philosophy of care and appropriate utilization in the United States
The following organizations also provide reliable health information.
●National Cancer Institute
1-800-4-CANCER
●American Society of Clinical Oncology
(www.cancer.net/portal/site/patient)
●Global Resource for Advancing Cancer Education (GRACE)
(https://cancergrace.org/treatments/lung-cancer)
●Lung Cancer Alliance
